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pubmed-article:15950245pubmed:issue18lld:pubmed
pubmed-article:15950245pubmed:dateCreated2005-8-22lld:pubmed
pubmed-article:15950245pubmed:abstractTextThe anticancer effect of 1-nitro-9-hydroxyethylamino acridine (C-857), a compound belonging to the 1-nitroacridine class, has been well documented. Despite its therapeutic efficacy, the clinical development of C-857 has been impeded partly due to its high systemic toxicity. In an effort to enhance antitumor efficacy and lower toxicity, derivatives of C-857 have been synthesized with substitutions made at position C-4 and/or an esterified hydroxyl group in side chain at the C-9 position. The introduction of a methyl group at C-4 resulted in C-1748, which has a significantly higher therapeutic efficacy and is being clinically developed as an anticancer agent for solid tumors. The present study was undertaken to correlate the mutagenicity of C-857, C-1748, C-1790, C-1872 and C-1873 with their cytotoxicity and their anti-tumor efficacy. The mutagenicity of these drugs was determined using three Ames Salmonella typhimurium strains TA1537, TA98 and TA102. The bacteria were treated with different molar concentrations, ranging from 10(-3) to 10(-12) M, of the drugs and drug-induced histidine revertants were then counted after a 48 h incubation. C-1748 did not induce any revertants in both TA1537 and TA98 at a dose of 10(-6) M, whereas, C-857 at the same dose induced approximately 842 and approximately 1034 revertants respectively. In TA102, mutagenicity was lower than observed with TA98 and TA1537 with highest revertants observed at 10(-5) M with C-857 (approximately 606) and C-1748 (approximately 108). Higher mutagenicity was observed in the derivatives C-1790, C-1872 and C-1873 compared to C-1748, but lower than C-857. These studies demonstrate that C-1748 has the least mutagenic potential, with a much higher antitumor effect in prostate cancer and is a promising chemotherapeutic agent for clinical development.lld:pubmed
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pubmed-article:15950245pubmed:authorpubmed-author:AshokBadithe...lld:pubmed
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pubmed-article:15950245pubmed:authorpubmed-author:NarayananRamk...lld:pubmed
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pubmed-article:15950245pubmed:pagination2312-23lld:pubmed
pubmed-article:15950245pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:15950245pubmed:year2005lld:pubmed
pubmed-article:15950245pubmed:articleTitleComparative analysis of mutagenic potency of 1-nitro-acridine derivatives.lld:pubmed
pubmed-article:15950245pubmed:affiliationNew York Medical College, Department of Microbiology and Immunology, Room 331, Basic Sciences Building, Valhalla, NY-10595, USA.lld:pubmed
pubmed-article:15950245pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15950245pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:15950245pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:15950245pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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